EBP

Summary: Refine inherited ER localization to ER membrane.

Reason: The literal PTHR14207 tree/MSA places the exact 230-residue target below PTN000368006; the relevant IBD is on that path. The EBPL-branch IRDs at PTN000368008 are outside the target path. A GO-slim display containing NOT ancestors is not substituted for those literal assertions. Independent human microscopy identifies ER membranes, and the human EBP crystal structure resolves five transmembrane helices. The older four-helix hydropathy prediction is historical rather than the current structural model.

Proposed replacements: endoplasmic reticulum membrane

Summary: Retain the inherited cholesterol-biosynthetic role.

Reason: The PTN001022122 cholesterol IBD lies on the target lineage and is grounded in human, mouse and rat evidence. Human EBP directly catalyzes a post-lanosterol sterol-isomerization step. The target occurring among descendant sources is appropriate experimental grounding, not circular evidence.

Summary: Retain the inherited fecosterol reaction as non-core substrate breadth.

Reason: The literal PTHR14207 tree/MSA places the exact 230-residue target below PTN000368006; the relevant IBD is on that path. The EBPL-branch IRDs at PTN000368008 are outside the target path. A GO-slim display containing NOT ancestors is not substituted for those literal assertions. The current term specifies fecosterol/episterol. Independent human-enzyme substrate assays establish this chemistry (PMID:12133002, Tables 3–4), so substrate naming does not justify rejection. It is retained as assay-supported breadth, separate from the physiological cholestenol core. The fecosterol tables were inspected in the author-uploaded original linked in the source guide; they are not included in the repository's abstract-only publication cache.

Summary: Refine the inherited isomerase reaction to cholestenol delta-isomerase.

Reason: The literal PTHR14207 tree/MSA places the exact 230-residue target below PTN000368006; the relevant IBD is on that path. The EBPL-branch IRDs at PTN000368008 are outside the target path. A GO-slim display containing NOT ancestors is not substituted for those literal assertions. GO:0004769 specifies 3-oxo-Delta5→Delta4 steroid isomerization, whereas the supported EBP reaction is a 3beta-hydroxy-sterol Delta8→Delta7 rearrangement. The positive isomerase evidence is preserved and represented with GO:0047750, rather than treating the original experimental or phylogenetic source as a wrong-gene citation. The definitions describe different reactions, not a parent/child pair.

Proposed replacements: cholestenol delta-isomerase activity

Summary: Refine nuclear-envelope localization to the observed nuclear membranes.

Reason: The native human microscopy identifies inner and outer nuclear-envelope membranes. This is a positive nuclear-membrane pool, not nucleoplasmic staining and not evidence of a distinct nuclear catalytic pathway. HPA independently assigns supported nuclear-membrane localization.

Proposed replacements: nuclear membrane

Summary: Retain the historical ER-membrane assertion.

Reason: Independent human microscopy identifies ER membranes, and the human EBP crystal structure resolves five transmembrane helices. The older four-helix hydropathy prediction is historical rather than the current structural model. This exact older GO_REF:0000044 source context is absent from the current export, which now includes a combined GO_REF:0000120 context; the biological assertion remains supported and its historical source is preserved.

Summary: Replace broad membrane localization with ER membrane.

Reason: The InterPro membrane assignment is biologically correct; breadth alone is not over-annotation. Independent native localization and integral-membrane structure support the more precise ER-membrane location, while separate nuclear/mitotic-vesicle assertions retain their own scope.

Proposed replacements: endoplasmic reticulum membrane

Summary: Refine general sterol metabolism to cholesterol biosynthesis.

Reason: EBP performs a sterol-isomerization step in the cholesterol-biosynthetic pathway. The broad InterPro process is true, and the more informative process is directly supported by enzyme chemistry and human genetic evidence.

Proposed replacements: cholesterol biosynthetic process

Summary: Retain mitotic cytoplasmic-vesicle localization.

Reason: The original Results describe EBP redistribution into vesicles during mitosis in activated human T lymphocytes, with return to ER/nuclear-envelope labeling late in mitosis. This is positive cell-cycle localization. It is retained as a contextual pool without asserting vesicle-specific catalysis. The source text and Figure 8 caption interchange panel-letter assignments for the two antibodies; this review relies on the stated EBP observation, not an independently inspected panel.

Summary: Retain cooperative cholesterol-epoxide hydrolase activity.

Reason: Human EBP and DHCR7 coexpression in COS-7 cells and knockdown experiments in MCF-7 cells support cooperative cholesterol-epoxide hydrolysis. The isolated catalytic/substrate-binding division of labor is not established; the data do not demonstrate purified EBP acting autonomously as a hydrolase. This positive complex-context activity is retained as a complementary non-core claim, without editing its imported qualifier.

Summary: Retain the reaction-specific cholestenol isomerase assignment.

Reason: The combined EC/Rhea/InterPro mapping corresponds to the established Delta8→Delta7 cholestenol reaction. Purified recombinant human EBP converts zymostenol-d7 to lathosterol-d7 in the 2019 assay. The assay is a biochemical reaction, not a measurement of native cellular flux.

Summary: Refine the positive CREB3 association by partner class.

Reason: The disease-variant Y2H screen compares sequence-verified human WT/mutant constructs; the three curated EBP–CREB3 records include no-effect substitutions. Its pairwise testing is positive, but a physiological ER transcription mechanism is not established. CREB3 is a DNA-binding bZIP transcription factor. The assayed O43889-2 is the displayed 371-residue product; the general FUNCTION and DNA-binding domain are present in the parent record. The interactor ROGID authenticates the referenced sequence; it is not proof that every fusion used the full-length protein. The refinement identifies binding to this independently classified partner; it does not transfer the partner’s activity to EBP, require binding to its active site, or assert a native pathway. GO:0140297 describes binding to a DNA-binding transcription factor; it does not require transcriptional regulation by the binding partner or membership of a nuclear transcription complex. The assayed association is retained at that binding-class scope.

Proposed replacements: DNA-binding transcription factor binding

Summary: Retain the historical heterogeneous HuRI interaction aggregate.

Reason: This historical source row aggregates the HuRI publication rather than specifying one partner. Its heterogeneous positive associations include enzymes, SNAREs, channels, receptors and incompletely characterized membrane proteins; a single binding subclass would not preserve that aggregate scope. The normal fetch attached TSNARE1 metadata to this old row, but that enrichment is separately archived and does not overwrite the historical source dictionary. Supported generic binding is retained under the explicit CLINGEN project policy.

Summary: Retain EBP self-association without fixing native oligomer stoichiometry.

Reason: The exact self-pair comprises three HuRI records, separate from the other partner records. Independent cross-linking and the 2019 crystal/coassociation experiments support EBP oligomerization. Different purified preparations have yielded different oligomer estimates; no obligatory native homodimer or tetramer is inferred. Self-association is retained as a non-core property alongside the catalytic core.

Summary: Retain the historical ortholog-derived fecosterol reaction.

Reason: The current term specifies fecosterol/episterol. Independent human-enzyme substrate assays establish this chemistry (PMID:12133002, Tables 3–4), so substrate naming does not justify rejection. It is retained as assay-supported breadth, separate from the physiological cholestenol core. The old GO_REF:0000107 source is preserved separately from the current combined electronic context. The fecosterol tables were inspected in the author-uploaded original linked in the source guide; they are not included in the repository's abstract-only publication cache.

Summary: Retain electronic cholesterol biosynthesis.

Reason: The electronic pathway assignment agrees with direct EBP sterol chemistry, human disease sterol profiles and the two explicit Reactome reaction branches.

Summary: Retain EBP participation in the Bloch cholesterol pathway.

Reason: The saved Reactome chain R-HSA-6807047→R-HSA-195690→catalyst 195674→human Q15125 encodes zymosterol isomerization at the ER membrane. Its catalyst GO label0004769 is chemically mismatched to the explicit substrate/product pair; that label discrepancy does not invalidate the pathway participation.

Summary: Retain EBP participation in the modified Kandutsch–Russell pathway.

Reason: The saved Reactome chain R-HSA-9969901→R-HSA-6807052→catalyst 195674→human Q15125 encodes zymostenol-to-lathosterol conversion at the ER membrane. Independent purified human EBP chemistry corroborates the step.

Summary: Preserve the positive isomerase evidence with a reaction-specific term.

Reason: The cached abstract was verified; full text was not recovered. It describes human CDPX2 variants and the tattered mouse. GO:0004769 specifies 3-oxo-Delta5→Delta4 steroid isomerization, whereas the supported EBP reaction is a 3beta-hydroxy-sterol Delta8→Delta7 rearrangement. The positive isomerase evidence is preserved and represented with GO:0047750, rather than treating the original experimental or phylogenetic source as a wrong-gene citation. The definitions describe different reactions, not a parent/child pair. Independent human biochemical evidence establishes the refined function, so this is not a rejection based on incomplete access.

Proposed replacements: cholestenol delta-isomerase activity

Summary: Preserve the positive isomerase evidence with a reaction-specific term.

Reason: The cached abstract was verified; full text was not recovered. It describes human sterol abnormalities and yeast complementation of human EBP variants. GO:0004769 specifies 3-oxo-Delta5→Delta4 steroid isomerization, whereas the supported EBP reaction is a 3beta-hydroxy-sterol Delta8→Delta7 rearrangement. The positive isomerase evidence is preserved and represented with GO:0047750, rather than treating the original experimental or phylogenetic source as a wrong-gene citation. The definitions describe different reactions, not a parent/child pair. Independent human biochemical evidence establishes the refined function, so this is not a rejection based on incomplete access.

Proposed replacements: cholestenol delta-isomerase activity

Summary: Refine the HPA ER observation to ER membrane by target-level synthesis.

Reason: HPA003130 gives supported ER localization in A-431, HaCaT and U2OS cells. The antibody has a multiple-gene-target warning and no image pixels were independently inspected. Native human immunogold/confocal evidence and the integral-membrane structure independently support ER membrane; this refinement does not claim that the HPA image alone resolves the membrane bilayer.

Proposed replacements: endoplasmic reticulum membrane

Summary: Retain the supported nuclear-membrane pool.

Reason: HPA reports nuclear-membrane localization as supported, specifically in HaCaT cells; the overall gene score is not used as a substitute for that per-location score. The antibody cross-target caution is explicit, and native human microscopy independently corroborates the pool. It is positive non-core localization relative to the demonstrated ER sterol-isomerization unit, not a rejected signal.

Summary: Retain experimentally observed mitotic vesicles.

Reason: The original Results describe EBP redistribution into vesicles during mitosis in activated human T lymphocytes, with return to ER/nuclear-envelope labeling late in mitosis. This is positive cell-cycle localization. It is retained as a contextual pool without asserting vesicle-specific catalysis. The source text and Figure 8 caption interchange panel-letter assignments for the two antibodies; this review relies on the stated EBP observation, not an independently inspected panel.

Summary: Retain the experimentally assigned cholestenol-isomerase function.

Reason: The abstract explicitly contrasts inactive EBPL with active human EBP controls, mutagenesis and chimeras. Its foreground EBPL title is not a wrong-gene argument. The full scanned body remained inaccessible, so detailed construct claims are not added; independent purified human EBP chemistry supports this established function.

Summary: Retain human EBP sterol-isomerase activity in a yeast assay.

Reason: The abstract states that human and mouse EBP cDNAs restore sterol-isomerase activity in yeast in vivo and in vitro. This is human-protein evidence in a yeast host, not a human-cell flux assay. Independent 2019 purified human EBP evidence confirms the reaction-specific term.

Summary: Retain the experimentally grounded cholestenol-isomerase reaction.

Reason: The PMID:9894009 abstract reports human EBP expression and mutational effects in sterol-isomerase-deficient yeast. Full original access remains unavailable; no unseen assay details or exact historical construct sequence are claimed. Independent 2019 purified human EBP supports the same core reaction. Historical residue numbering is not silently harmonized with the current sequence.

Summary: Retain native ER-membrane localization.

Reason: The original human-cell confocal/immunogold observations support ER membranes. The imported qualifier is preserved without inferring that microscopy separately measured catalysis at each labeled membrane. Sterol chemistry and structure independently support the integrated ER catalytic location.

Summary: Retain the experimentally supported cooperative ChEH activity.

Reason: Human EBP and DHCR7 coexpression in COS-7 cells and knockdown experiments in MCF-7 cells support cooperative cholesterol-epoxide hydrolysis. The isolated catalytic/substrate-binding division of labor is not established; the data do not demonstrate purified EBP acting autonomously as a hydrolase. This positive complex-context activity is retained as a complementary non-core claim, without editing its imported qualifier.

Summary: Preserve the positive isomerase evidence with a reaction-specific term.

Reason: The cached abstract was verified; full text was not recovered. It describes human sterol abnormalities and yeast complementation of human EBP variants. GO:0004769 specifies 3-oxo-Delta5→Delta4 steroid isomerization, whereas the supported EBP reaction is a 3beta-hydroxy-sterol Delta8→Delta7 rearrangement. The positive isomerase evidence is preserved and represented with GO:0047750, rather than treating the original experimental or phylogenetic source as a wrong-gene citation. The definitions describe different reactions, not a parent/child pair. Independent human biochemical evidence establishes the refined function, so this is not a rejection based on incomplete access.

Proposed replacements: cholestenol delta-isomerase activity

Summary: Preserve the positive isomerase evidence with a reaction-specific term.

Reason: The cached abstract was verified; full text was not recovered. It describes human sterol abnormalities and yeast complementation of human EBP variants. GO:0004769 specifies 3-oxo-Delta5→Delta4 steroid isomerization, whereas the supported EBP reaction is a 3beta-hydroxy-sterol Delta8→Delta7 rearrangement. The positive isomerase evidence is preserved and represented with GO:0047750, rather than treating the original experimental or phylogenetic source as a wrong-gene citation. The definitions describe different reactions, not a parent/child pair. Independent human biochemical evidence establishes the refined function, so this is not a rejection based on incomplete access.

Proposed replacements: cholestenol delta-isomerase activity

Summary: Retain ER membrane while updating the topology context.

Reason: The cloning-paper abstract predicted four membrane segments; that historical prediction is preserved in the inherited excerpt. Native human localization and the later five-transmembrane-helix structure independently establish ER membrane. The predicted helix count is not presented as the current structural conclusion.

Summary: Refine cholesterol metabolism to the demonstrated biosynthetic step.

Reason: The patient sterol profiles and functional complementation place EBP in cholesterol biosynthesis. This specific process captures the enzymatic step rather than merely a downstream effect of altered cholesterol levels.

Proposed replacements: cholesterol biosynthetic process

Summary: Retain the developmental ossification consequence as non-core.

Reason: Human CDPX2 genetics supports the existing curated skeletal-development association. The abstract connects the sterol defect with bone development; inaccessible full text is not grounds to reject that experimental annotation. The evidence does not establish a separate EBP ossification catalyst, so it remains a contextual developmental consequence of sterol metabolism.

Summary: Retain curated similarity support for substrate breadth.

Reason: The current term specifies fecosterol/episterol. Independent human-enzyme substrate assays establish this chemistry (PMID:12133002, Tables 3–4), so substrate naming does not justify rejection. It is retained as assay-supported breadth, separate from the physiological cholestenol core. The literal donor lineage and current donor annotations are preserved without treating donor count as evidence quality. The fecosterol tables were inspected in the author-uploaded original linked in the source guide; they are not included in the repository's abstract-only publication cache.

Summary: Represent the human-protein yeast assay with the correct reaction term.

Reason: The source abstract supports Delta8→Delta7 sterol isomerization, not the current GO:0004769 reaction definition. GO:0004769 specifies 3-oxo-Delta5→Delta4 steroid isomerization, whereas the supported EBP reaction is a 3beta-hydroxy-sterol Delta8→Delta7 rearrangement. The positive isomerase evidence is preserved and represented with GO:0047750, rather than treating the original experimental or phylogenetic source as a wrong-gene citation. The definitions describe different reactions, not a parent/child pair. No unavailable full-text details are inferred.

Proposed replacements: cholestenol delta-isomerase activity

Summary: Refine the observed nuclear envelope to nuclear membrane.

Reason: Original human microscopy places EBP on the inner and outer nuclear-envelope membranes. The more precise nuclear-membrane term retains that positive compartment without asserting nucleoplasmic localization or nuclear-specific catalysis.

Proposed replacements: nuclear membrane

Summary: Refine the native ER observation to ER membrane.

Reason: Original human immunogold/confocal observations and the later integral-membrane structure support the more precise membrane location. Separate nuclear-envelope and mitotic-vesicle source contexts remain represented.

Proposed replacements: endoplasmic reticulum membrane

Summary: Retain cholesterol biosynthesis with the heterologous assay scope explicit.

Reason: PMID:9894009 examines human EBP in a yeast sterol assay. It establishes human-protein isomerase function; it does not directly measure cholesterol flux in human cells. Human patient sterol profiles and independently demonstrated sterol chemistry support the gene-level cholesterol-biosynthetic role.

Summary: Retain the modeled ER-membrane reaction location.

Reason: The exact R-HSA-195690 catalyst chain reaches human Q15125 residues 2–230 in the ER membrane. Native human microscopy independently supports this compartment. The pathway model is treated as a curated reaction/context assertion, not a new microscopy experiment.

Summary: Retain the modeled ER-membrane reaction location.

Reason: The exact R-HSA-6807052 catalyst chain reaches human Q15125 residues 2–230 in the ER membrane. Native human microscopy independently supports this compartment. The pathway model is treated as a curated reaction/context assertion, not a new microscopy experiment.

Summary: Retain the current combined electronic substrate-breadth assertion.

Reason: The current term specifies fecosterol/episterol. Independent human-enzyme substrate assays establish this chemistry (PMID:12133002, Tables 3–4), so substrate naming does not justify rejection. It is retained as assay-supported breadth, separate from the physiological cholestenol core. This is a current imported source context, not an authored NEW annotation. The fecosterol tables were inspected in the author-uploaded original linked in the source guide; they are not included in the repository's abstract-only publication cache.

Summary: Retain the positive TMEM120B association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM120B is associated with adipogenesis and is explicitly not established as an ion channel. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive TMEM218 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM218 has a ciliary-biogenesis association without an established binding-class activity. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive TUSC5 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TUSC5 lacks a sufficiently resolved molecular class for a narrower binding term. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive SMIM1 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. SMIM1 is a membrane regulator of erythrocyte formation; that process role does not establish a transporter or receptor class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive C2CD2L association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. C2CD2L is a nonvesicular phospholipid-transfer protein; this is not evidence that the partner is a transmembrane transporter. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive GOSR2 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. GOSR2 is a vesicle-fusion SNARE component. Recorded construct features: mutation with no effect:144-144|gal4 dna binding domain:n-n. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: SNARE binding

Summary: Refine the positive CDIPT association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. CDIPT catalyzes phosphatidylinositol synthesis. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: enzyme binding

Summary: Refine the positive TIMM23 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. TIMM23 forms the mitochondrial inner-membrane protein-translocation channel. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: transmembrane transporter binding

Summary: Refine the positive STX7 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. STX7 is a syntaxin-family SNARE. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: syntaxin binding

Summary: Retain the positive CYB5B association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. CYB5B is an electron-transfer carrier, rather than an independently catalytic enzyme in the reviewed record. Recorded construct features: sufficient binding region:5-150. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive STX6 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. STX6 is a syntaxin-family SNARE. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: syntaxin binding

Summary: Retain the positive SYNGR1 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. SYNGR1 is a synaptic-vesicle membrane protein; vesicle location alone does not make it a SNARE. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive VAMP4 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. VAMP4 is a vesicular SNARE. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: SNARE binding

Summary: Refine the positive SEC22B association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. SEC22B is an ER/Golgi trafficking SNARE. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: SNARE binding

Summary: Retain the positive YIF1A association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. YIF1A is a membrane-trafficking factor without a warranted narrower binding subclass here. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive ZFPL1 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. ZFPL1 participates in Golgi organization; its zinc-finger name does not establish a DNA-binding transcription-factor class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive NDUFA3 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. NDUFA3 is an accessory respiratory-complex subunit, not an independently assigned oxidoreductase catalyst. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive VAPB association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. VAPB is a membrane-contact/trafficking organizer; its name does not identify it as a vesicular SNARE. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive BMP10 association without an unresolved partner-class refinement.

Reason: The positive human Y2H pair is retained. The assayed reference is a 424-residue BMP10 precursor with a separately processed propeptide at residues 22–316 and mature cytokine at 317–424. The interaction does not distinguish these separate products. The narrower cytokine-binding claim is therefore left unassigned. This uncertainty concerns the molecular region and processing state, not a requirement for native signaling or secretion in every binding assay.

Summary: Refine the positive GJB6 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. GJB6 is a gap-junction channel protein. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: transmembrane transporter binding

Summary: Refine the positive ABHD16A association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. ABHD16A is a phosphatidylserine lipase. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: enzyme binding

Summary: Retain the positive C5 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. The literal C5 precursor yields products with different roles, including C5a and C5b. These records do not resolve binding to a processed cytokine product, so cytokine binding is not assigned to this precursor-level pair. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive GYPA association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. GYPA is an erythrocyte membrane glycoprotein; membrane structural support alone does not establish membership in the actin, microtubule or intermediate-filament cytoskeleton. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive C2 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. C2 contains the serine-protease catalytic component of complement convertases. The screen does not establish proteolytic activation or a particular cleaved product. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: protease binding

Summary: Retain the positive THBD association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. THBD is a thrombin cofactor/receptor whose own catalytic enzyme activity is not established. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive SLC3A2 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. The former P08195-4 identity is resolved: the 661-residue historical sequence matches the record ROGID, and its assayed 133–661 region equals the current 529-residue displayed SLC3A2 sequence. SLC3A2 is an auxiliary amino-acid-transporter heavy chain/trafficking factor; binding to it does not by itself establish binding to an assembled transmembrane transport complex. Recorded construct features: sufficient binding region:133-661. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive PVR association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. PVR is a cell-adhesion/viral-entry receptor. The reviewed source does not establish the ligand-to-cell-signaling receptor class required for a narrower signaling-receptor-binding term. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive TMEM11 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM11 contributes to mitochondrial morphology without a sufficiently established narrower binding-class activity. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive CES1 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. CES1 is a carboxylesterase; the assayed isoform 3 deletes one residue outside the annotated catalytic triad and retains the catalytic domain. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: enzyme binding

Summary: Refine the positive VAMP1 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. VAMP1 is a vesicular SNARE. The assayed short C-terminal variant retains the SNARE domain; no equivalence of membrane anchoring is inferred. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: SNARE binding

Summary: Refine the positive CD40 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. CD40 is a ligand-activated TNF-receptor-family signaling receptor. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway. GO:0005102 classifies binding to a signaling receptor. Its ontology comment separately recommends considering receptor agonist activity where appropriate; receptor activation is not a requirement of this binding term. The positive pair and independently established receptor identity support this limited refinement.

Proposed replacements: signaling receptor binding

Summary: Refine the positive GJB2 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. GJB2 is a gap-junction channel protein. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: transmembrane transporter binding

Summary: Refine the positive HMOX2 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. HMOX2 catalyzes heme oxidation. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: enzyme binding

Summary: Refine the positive PTPN9 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. PTPN9 is a protein tyrosine phosphatase. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: protein phosphatase binding

Summary: Refine the positive CYB561 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. CYB561 catalyzes transmembrane electron-transfer reduction reactions. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: enzyme binding

Summary: Refine the positive MMP14 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. MMP14 is a zinc-dependent matrix metalloprotease. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: protease binding

Summary: Retain the positive PNLIPRP1 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. PNLIPRP1 is explicitly an inactive lipase-related protein; enzyme binding would incorrectly infer catalysis from family membership. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive EMP1 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. EMP1 is a membrane protein associated with cell growth/adhesion, without a resolved narrower molecular class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive TMBIM6 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. TMBIM6 is an ER calcium-leak channel. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: transmembrane transporter binding

Summary: Retain the positive SYNJ2BP association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. SYNJ2BP is a membrane-tethering adaptor; no narrower reviewed binding term is established by that role. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive CD81 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. CD81 is a tetraspanin membrane organizer/co-receptor. This record does not resolve a standalone signaling receptor activity for the assayed pair. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive STX1B association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. STX1B is a syntaxin1-family SNARE. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: syntaxin-1 binding

Summary: Refine the positive VAMP2 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. VAMP2 is a vesicular SNARE. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: SNARE binding

Summary: Refine the positive CYP4F2 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. CYP4F2 is a cytochrome-P450 hydroxylase. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: enzyme binding

Summary: Retain the positive DEFB103A association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. DEFB103A is an antimicrobial peptide with immunomodulatory effects; the present evidence does not justify recasting this precursor-level interaction as a cytokine-binding assay. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive PMP22 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. PMP22 is a myelin membrane component; that location does not establish a cytoskeletal or transporter class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive PLP2 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. PLP2 is a membrane protein whose precise channel/transport assignment is insufficiently resolved here. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive CD69 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. CD69 is a signaling receptor with independently described ligand-dependent immune-cell effects. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway. GO:0005102 classifies binding to a signaling receptor. Its ontology comment separately recommends considering receptor agonist activity where appropriate; receptor activation is not a requirement of this binding term. The positive pair and independently established receptor identity support this limited refinement.

Proposed replacements: signaling receptor binding

Summary: Refine the positive EHHADH association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. EHHADH carries enoyl-CoA hydratase and hydroxyacyl-CoA dehydrogenase catalytic activities. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: enzyme binding

Summary: Retain the positive SMAGP association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. SMAGP is a membrane glycoprotein involved in cell adhesion, without a warranted narrower binding subclass. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive BNIP3 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. BNIP3 is a mitophagy/apoptosis regulator; the1–194 assayed region does not establish a more informative partner class. Recorded construct features: sufficient binding region:1-194. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive STX5 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. STX5 is a syntaxin-family SNARE; the assayed 55–355 region retains its syntaxin/SNARE machinery. Recorded construct features: sufficient binding region:55-355. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: syntaxin binding

Summary: Refine the positive AQP6 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. AQP6 is an anion-conducting membrane channel. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: transmembrane transporter binding

Summary: Refine the positive FKBP8 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. FKBP8 is a peptidyl-prolyl isomerase; the assayed 58–412 region retains its catalytic domain. Recorded construct features: sufficient binding region:58-412. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: enzyme binding

Summary: Retain the positive FXYD3 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. FXYD3 regulates Na/K-ATPase and is not the catalytic transporter subunit. The 58–144 region of the literal variant maps to the current 87-residue product. Recorded construct features: sufficient binding region:58-144; sufficient binding region:58-144|gal4 dna binding domain:n-n. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive VAMP3 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. VAMP3 is a vesicular SNARE. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: SNARE binding

Summary: Retain the positive NKG7 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. NKG7 is a granule membrane protein; granule biology does not imply a SNARE or enzyme class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive LTC4S association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. LTC4S catalyzes leukotriene-C4 synthesis. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: enzyme binding

Summary: Retain the positive ODF4 association without an unresolved partner-class refinement.

Reason: The positive human Y2H pair is retained. The available ODF4 record describes a possible sperm outer-dense-fiber role by similarity and predicts a multipass membrane protein. It does not establish ODF4 as a protein component of the actin, microtubule or intermediate-filament cytoskeleton specified by GO:0008092. The outer-dense-fiber name alone is insufficient for that refinement.

Summary: Refine the positive SLC35G1 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. SLC35G1 is a chloride-sensitive citrate transporter; this class is independently supported without attributing citrate transport to EBP. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: transmembrane transporter binding

Summary: Retain the positive ARL13B association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. ARL13B is a GTP-binding regulatory protein, but the curated record leaves intrinsic GTP hydrolysis unresolved. GTPase binding requires an established hydrolyzing partner, not its family name alone. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive ORMDL2 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. ORMDL2 regulates sphingolipid synthesis rather than catalyzing the lipid reaction. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive UNC50 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. UNC50 is a membrane-trafficking factor with no warranted narrower binding class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive TMEM97 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM97 is a sterol-homeostasis ligand-binding protein; its sigma-receptor name alone does not establish the ligand-to-signaling mechanism required for the selected receptor-binding subclass. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive MS4A13 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. MS4A13 has no sufficiently resolved molecular activity for a narrower class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive FAM209A association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. FAM209A has no sufficiently resolved molecular activity for a narrower class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive RTP2 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. RTP2 promotes receptor trafficking rather than being the signaling receptor itself. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive LDLRAD1 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. LDLRAD1 has a receptor-associated domain name but no sufficiently established receptor activity in the reviewed record. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive TSPO2 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TSPO2 participates in sterol handling; translocator nomenclature is not proof of a substrate-translocation mechanism. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive LEMD1 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. LEMD1 is a nuclear-envelope-associated membrane protein; this does not establish a DNA-binding transcription-factor class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive TMEM42 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM42 has no sufficiently resolved molecular activity for a narrower class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive SLC48A1 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. SLC48A1 transports heme across membranes. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: transmembrane transporter binding

Summary: Retain the positive TMEM65 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM65 has context-dependent channel/regulatory claims; the63–240 pair is retained without forcing a disputed transporter class. Recorded construct features: sufficient binding region:63-240. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive C5orf46 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. C5orf46 is incompletely characterized; the1–72 assayed region is preserved without a narrower class. Recorded construct features: sufficient binding region:1-72. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive SNORC association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. SNORC is a small membrane protein without an established narrower binding class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive ZDHHC24 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. ZDHHC24 is described as a probable palmitoyltransferase. The saved evidence does not independently establish catalysis beyond the family assignment. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive MFSD6 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. MFSD6 has a viral-entry receptor role for its assayed329–791 region; that does not establish a signaling-receptor class or transmembrane transport activity. Recorded construct features: sufficient binding region:329-791. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive FA2H association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. FA2H is a fatty-acid hydroxylase. The assayed 93–372 region retains the hydroxylase domain while excluding the N-terminal cytochrome-b5 domain; full catalytic equivalence of that fragment is not claimed. Recorded construct features: sufficient binding region:93-372. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: enzyme binding

Summary: Refine the positive LPCAT2 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. LPCAT2 is a lysophosphatidylcholine acyltransferase. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: enzyme binding

Summary: Refine the positive OTOP3 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. OTOP3 is a proton channel. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: transmembrane transporter binding

Summary: Retain the positive LRP10 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. LRP10 is an endocytic sorting receptor; a signaling-receptor subclass is not inferred from uptake alone. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive HSD17B13 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. HSD17B13 has demonstrated dehydrogenase activities; disagreement about retinol as a substrate does not eliminate its independently established enzyme class. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: enzyme binding

Summary: Retain the positive ANKRD46 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. The displayed ANKRD46 product is preserved, but ankyrin repeats do not specify a more informative binding class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive STX12 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. STX12 is a syntaxin-family SNARE. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: syntaxin binding

Summary: Refine the positive SLC30A8 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. SLC30A8 is a zinc/proton antiporter; the assayed 50–369 region retains the transporter domain. Recorded construct features: sufficient binding region:50-369. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: transmembrane transporter binding

Summary: Retain the positive NRM association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. NRM is a nuclear-membrane protein without a resolved narrower partner class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive PLPP6 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. PLPP6 is a lipid phosphatase. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: phosphatase binding

Summary: Retain the positive ORMDL3 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. ORMDL3 regulates sphingolipid synthesis rather than catalyzing it. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive SYS1 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. SYS1 is a Golgi trafficking protein without a warranted narrower class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive TMEM86A association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. TMEM86A catalyzes lysoplasmalogen hydrolysis. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: enzyme binding

Summary: Retain the positive VMA12 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. VMA12 assists vacuolar ATPase assembly; it is not the ATPase catalyst. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive JAGN1 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. JAGN1 is an ER organization/secretion factor, not an established enzyme or transporter. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive TMEM86B association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. TMEM86B catalyzes lysoplasmalogen hydrolysis. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: enzyme binding

Summary: Retain the positive SERP2 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. SERP2 is a stress-associated ER protein; protection of nascent proteins alone does not resolve a folding-chaperone activity for this partner. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive ARL6IP6 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. ARL6IP6 is a membrane organization factor without a warranted narrower binding class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive RNF152 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. RNF152 is an E3 ubiquitin-protein ligase. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: ubiquitin protein ligase binding

Summary: Retain the positive TMEM229B association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM229B has no sufficiently resolved molecular activity for a narrower class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive CLDND2 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. CLDND2 has a claudin-like domain but no established narrower molecular class here. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive CCL4L1 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. CCL4L1 is a chemokine. The class refinement does not establish secretion or native chemotactic activity of the assayed pair. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway. The independently classified chemokine reference sequence is represented in the exact pair record. GO:0019956 describes binding to that partner class; it does not require chemotaxis by EBP, secretion in the assay, or a mapped binding interface.

Proposed replacements: chemokine binding

Summary: Retain the positive TMEM254 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM254 has no sufficiently resolved molecular activity for a narrower class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive SFXN5 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. SFXN5 has a curated mitochondrial transporter assignment, including citrate transport by similarity; it is explicitly not assigned serine transport. This identifies the partner class rather than an EBP transport function. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: transmembrane transporter binding

Summary: Refine the positive GPR152 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. GPR152 is an orphan G-protein-coupled receptor; the refinement identifies the receptor class without assigning an endogenous ligand or EBP agonism. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway. GO:0005102 classifies binding to a signaling receptor. Its ontology comment separately recommends considering receptor agonist activity where appropriate; receptor activation is not a requirement of this binding term. The positive pair and independently established receptor identity support this limited refinement.

Proposed replacements: signaling receptor binding

Summary: Retain the positive BTN2A2 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. BTN2A2 is an immune regulatory ligand; it is not automatically a signaling receptor itself. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive ARLN association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. The short ARLN isoform regulates SERCA; it is not the calcium-pump catalyst. Recorded construct features: sufficient binding region:134-199. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive TMEM239 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. The literal TMEM239 isoform and2–152 region are retained without an established narrower molecular class. Recorded construct features: sufficient binding region:2-152. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive GIMAP1 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. GIMAP1 binds guanine nucleotides, but the saved functional evidence does not independently establish intrinsic GTP hydrolysis for the narrower GTPase-binding definition. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive NINJ1 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. NINJ1 has membrane adhesion/rupture roles; these do not identify a selected narrower binding class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive SCAMP4 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. SCAMP4 participates in membrane traffic without a sufficiently established narrower molecular class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive TMEM203 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM203 regulates calcium homeostasis, which does not itself establish ion translocation. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive LRRC59 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. LRRC59 is a membrane-associated assembly/trafficking factor without a warranted narrower binding class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive CREB3L1 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. CREB3L1 is a DNA-binding bZIP transcription factor. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway. GO:0140297 describes binding to a DNA-binding transcription factor; it does not require transcriptional regulation by the binding partner or membership of a nuclear transcription complex. The assayed association is retained at that binding-class scope.

Proposed replacements: DNA-binding transcription factor binding

Summary: Refine the positive TBC1D20 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. TBC1D20 is a Rab-family GTPase-activating protein. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: GTPase activating protein binding

Summary: Retain the positive TLCD1 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TLCD1 is involved in membrane lipid homeostasis without a resolved catalytic activity. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive YIPF6 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. YIPF6 participates in membrane trafficking without an established narrower class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive GIMAP5 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. GIMAP5 is a guanine-nucleotide-binding regulatory protein; GTPase-family naming is not substituted for an independent hydrolysis assignment. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive SLC35A4 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. SLC35A4 has curated CDP-ribitol transport activity; a membrane-transporter binding class is supported without assigning substrate transport to EBP. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: transmembrane transporter binding

Summary: Retain the positive RUSF1 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. RUSF1 has no sufficiently established narrower molecular class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive FAXDC2 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. FAXDC2 has a fatty-acid-hydroxylase-like domain but the reviewed evidence does not establish a specific catalytic reaction. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive SLC41A2 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. SLC41A2 transports divalent cations; the assayed 84–573 region retains its transporter domain. Recorded construct features: sufficient binding region:84-573. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: transmembrane transporter binding

Summary: Retain the positive DNAJC30 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. DNAJC30 promotes mitochondrial complex-I repair; that role does not establish a conventional protein-folding chaperone activity or ATPase activity. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive TLCD4 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TLCD4 has no sufficiently resolved molecular activity for a narrower class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive NEU1 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. NEU1 is a sialidase. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: enzyme binding

Summary: Retain the positive YIPF4 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. YIPF4 participates in membrane trafficking without a warranted narrower class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive TMEM208 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM208 has no sufficiently established narrower molecular class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive TMEM243 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM243 has no sufficiently established narrower molecular class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive EMC6 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. EMC6 is a subunit of the membrane-protein insertase complex. This pair does not identify binding to an assembled transporter or an independently transporting EMC6 product. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive TMEM147 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM147 is a translocon-associated BOS-complex subunit; its assembly role does not establish an independently transporting partner. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive FUNDC2 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. FUNDC2 is a membrane regulatory protein; an incompletely established nuclear transcription role is not used for a transcription-factor-binding refinement. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive SFXN3 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. SFXN3 is a sideroflexin amino-acid transporter. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: transmembrane transporter binding

Summary: Retain the positive TMEM120A association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM120A has disputed channel/metabolic assignments; the verified pair is retained without choosing among those unresolved classes. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive SMIM3 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. SMIM3 has no sufficiently established narrower molecular class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive FXYD6 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. FXYD6 regulates an ion pump rather than supplying the pump catalytic machinery. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive TMEM222 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM222 has no sufficiently resolved molecular activity; its 21–208 assayed region remains explicit. Recorded construct features: sufficient binding region:21-208; sufficient binding region:21-208|gal4 dna binding domain:n-n. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive UNC93B1 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. UNC93B1 traffics innate immune receptors rather than being the signaling receptor itself. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive DEFB127 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. DEFB127 is an antimicrobial peptide, without an established cytokine-class inference for this pair. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive ARV1 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. ARV1 is involved in lipid homeostasis; a concrete transport mechanism is not established for this binding-class inference. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive TMEM60 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM60 has no sufficiently resolved molecular activity; the3–133 region is preserved. Recorded construct features: sufficient binding region:3-133. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive CHODL association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. CHODL is a membrane C-type lectin/adhesion protein without a sufficiently established signaling-receptor class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive ATP13A1 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. The literal ATP13A1 isoform C is 344 residues and lacks canonical residues 1–860, including most ATPase/translocase machinery. The full-length protein class is not transferred to this truncated product. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive SMCO4 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. SMCO4 has no sufficiently established narrower molecular class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive TMEM167B association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM167B is a membrane-trafficking factor without a warranted narrower class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive TREX1 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. TREX1 is a DNA exonuclease; the assayed N-terminally extended isoform 1 retains the exonuclease domain. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: enzyme binding

Summary: Refine the positive SACM1L association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. SACM1L is a phosphatidylinositol phosphatase. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: phosphatase binding

Summary: Retain the positive TMEM14B association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM14B has no sufficiently established narrower molecular class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive TMEM140 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM140 has no sufficiently established narrower molecular class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive TMEM100 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM100 modulates channel signaling but is not independently established as the transporter. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive SLC38A7 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. SLC38A7 is a sodium-coupled amino-acid transporter. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: transmembrane transporter binding

Summary: Retain the positive TMEM51 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM51 has no sufficiently established narrower molecular class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive TMEM242 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM242 organizes respiratory-complex assembly rather than catalyzing ATP synthesis. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive NDUFB11 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. NDUFB11 is an accessory respiratory-complex subunit, not the oxidoreductase catalytic subunit. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive USE1 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. USE1 is an ER vesicle-fusion SNARE. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: SNARE binding

Summary: Retain the positive NINJ2 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. NINJ2 is a membrane adhesion protein without a warranted narrower molecular class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive CCDC167 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. CCDC167 has no sufficiently established narrower molecular class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive VAPA association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. VAPA is a membrane-contact organizer; the8–249 region is not classified as a SNARE merely from its name. Recorded construct features: sufficient binding region:8-249. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive ORMDL1 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. ORMDL1 regulates sphingolipid synthesis rather than catalyzing it. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive TMEM14C association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. TMEM14C is involved in porphyrin/heme metabolism, but the precise transporter mechanism is not sufficiently established here. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive FETUB association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. FETUB is a protease inhibitor rather than a protease. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive NAT8 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. NAT8 is an N-acetyltransferase; the assayed 1–226 region differs only by omission of the final residue. Recorded construct features: sufficient binding region:1-226. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: enzyme binding

Summary: Retain the positive ERG28 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. ERG28 organizes sterol-biosynthetic enzymes but is not itself an established catalytic enzyme. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive STX8 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. STX8 is a syntaxin-family SNARE. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: syntaxin binding

Summary: Retain the positive ERGIC3 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. ERGIC3 is an ER-Golgi trafficking protein without a warranted narrower binding class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive PLLP association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. PLLP is a membrane organization protein without a sufficiently established transporter class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive UBE2J1 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. UBE2J1 is an E2 ubiquitin-conjugating enzyme. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: ubiquitin conjugating enzyme binding

Summary: Retain the positive FIS1 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. FIS1 is an organelle-fission adaptor rather than the dynamin GTPase catalyst. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive YIPF1 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. YIPF1 participates in membrane trafficking without a warranted narrower class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive INSIG2 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. INSIG2 is a sterol-sensing regulator rather than a sterol-isomerase catalyst. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the positive IER3IP1 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. IER3IP1 is a membrane homeostasis factor without a warranted narrower class. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Refine the positive UBIAD1 association by partner class.

Reason: The exact human pair is positive, sequence-confirmed Y2H evidence. UBIAD1 is a prenyltransferase. This identifies partner-class binding, without transferring the partner activity to EBP or claiming pair-specific orthogonal validation, active-site contact or a native pathway.

Proposed replacements: enzyme binding

Summary: Retain the positive SERP1 association with bounded functional scope.

Reason: The exact human Y2H association is retained under the project’s positive-binding exception. SERP1 stabilizes nascent membrane proteins during stress; a specific folding-chaperone class is not established by the saved target evidence. A narrower class is not established; no native mechanism or pair-specific orthogonal validation is asserted.

Summary: Retain the current combined ER-membrane mapping.

Reason: The literal mouse/Ensembl and UniProt subcellular-location mapping agrees with native human microscopy and EBP membrane structure. It is kept distinct from the older historical GO_REF:0000044 row.

Summary: Refine broad carbon–carbon double-bond isomerization.

Reason: The mouse-derived electronic assertion is biologically correct but broad. Direct human EBP chemistry supports the specific cholestenol Delta8→Delta7 isomerase term; no target-specific functional loss or donor error is alleged.

Proposed replacements: cholestenol delta-isomerase activity